tbuckley/cabot-search huggingface dataset:
Mesoporous Silica Nanoparticles‐Based Nanoplatforms: Basic Construction, Current State, and Emerging Applications in Anticancer Therapeutics
Authors: Yi Feng, Zhen Liao, Mengyue Li, Hanxi Zhang, Tingting Li, Xiang Qin, Shun Li, Chunhui Wu, Fengming You, Xiaoling Liao, Lulu Cai, Hong Yang, Yiyao Liu
Journal: Advanced Healthcare Materials (2022)

In recent years, researchers are developing novel nanoparticles for diagnostic applications using imaging techniques and for therapeutic purposes through drug delivery techniques. The unique physical and chemical properties of mesoporous silica nanoparticles (MSNs) make it possible to integrate a variety of commonly used therapeutic and imaging agents to construct a multimodal synergistic anticancer drug delivery system. Herein, recent advances in MSNs synthesis for drug delivery and smart response applications are reviewed. First, synthetic strategies for the fabrication of ordered MSNs, hollow MSNs, core-shell structured MSNs, dendritic MSNs, and biodegradable MSNs are outlined. Then, the recent research progress in designing functional MSN materials with various controlled release mechanisms in anticancer therapy is discussed, and new properties are introduced to suggest the latest design requirements as drug delivery materials. The review also highlights significant achievements in bioimaging using MSNs and their multifunctional counterparts as delivery vehicles. Finally, personal views on key directions for future work in this area are presented.
Editorial expression of concern: Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma
Authors: Fei Wang, Jin-Lian Yang, Ke-ke Yu, Mei Xu, You-zhi Xu, Li Chen, Yan-min Lu, Hao-shu Fang, Xin-yi Wang, Zhong-qian Hu, Fei-fei Li, Lixin Kan, Jia Luo, Si-Ying Wang
Journal: Molecular Cancer (2022)
Race- and Neighborhood-Related Disparities Spanning the COVID-19 Pandemic: Trajectories of Combined Glycemic Control and BMI in Youth With Diabetes
Authors: Mary Ellen Vajravelu, Iswariya Mani, Shehryar Malik, Brianna Hewitt, Vaishnavi Peyyety, Silva Arslanian
Journal: Diabetes Care (2022)

OBJECTIVE To use combined glycemic (HbA1c) and BMI z-score (BMIZ) trajectories spanning the coronavirus disease 2019 (COVID-19) pandemic to identify high-risk subgroups of adolescents with diabetes. RESEARCH DESIGN AND METHODS Retrospective cohort of adolescents 10–19 years old with type 1 and type 2 diabetes with one or more visits at a large pediatric hospital from January 2018 through February 2020 (prepandemic) and April 2020 through August 2021 (pandemic). Group-based trajectory models were used to identify latent classes of combined BMIZ and HbA1c trajectories. Multinomial logistic regression was used to evaluate predictors of class membership, including Area Deprivation Index (ADI) (socioeconomic status proxy). RESULTS The cohort included 1,322 youth with type 1 diabetes (93% White and 7% Black) and 59 with type 2 diabetes (53% Black and 47% White). For type 1 diabetes, six trajectory classes emerged. Black youth were more likely to be in the class with worsening glycemic control and concurrent BMIZ decrease at pandemic onset (relative risk ratio [RRR] vs. White: 3.0 [95% CI 1.3–6.8]) or in the class with progressively worsening glycemic control and obesity (RRR 3.0 [95% CI 1.3–6.8]), while those from the most deprived neighborhoods (RRR ADI tertile 3 vs. 1: 1.9 [95% CI 1.2–2.9]) were more likely to be in the class with stable obesity and glycemic control. For type 2 diabetes, three distinct trajectories emerged, two of which experienced worsening glycemic control with concurrent BMIZ decline at pandemic onset. CONCLUSIONS Race and neighborhood deprivation were independently associated with distinct glycemic and BMIZ trajectory classes in youth with diabetes, highlighting persistent and widening disparities associated with the COVID-19 pandemic.
Fat Fuels the Fire in Cervical Cancer
Authors: Kassidy M. Jungles, Michael D. Green
Journal: Cancer Research (2022)

Cervical cancer is the second most common cause of cancer mortality among young women and disproportionately impacts underserved patient populations. An obesity paradox has been observed in cervical cancer wherein patients with higher body mass indices benefit more from standard-of-care chemoradiation. However, the molecular pathways through which obesity modulates treatment response are poorly defined. In exciting work in this issue of Cancer Research, Muhammad and colleagues have shown that monounsaturated and diunsaturated free fatty acids released by adipocytes activate β-oxidation within tumor cells, which potentiates radiotherapy. This work extends our understanding of the metabolic vulnerabilities of cervical cancer. See related article by Muhammad et al., p. 4515.
Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells
Authors: Iris van 't Erve, Jamie E. Medina, Alessandro Leal, Eniko Papp, Jillian Phallen, Vilmos Adleff, Elaine Jiayuee Chiao, Adith S. Arun, Karen Bolhuis, John K. Simmons, Aanavi Karandikar, Kenneth C. Valkenburg, Mark Sausen, Samuel V. Angiuoli, Robert B. Scharpf, Cornelis J.A. Punt, Gerrit A. Meijer, Victor E. Velculescu, Remond J.A. Fijneman
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Circulating tumor DNA (ctDNA) has the potential to guide therapy selection and monitor treatment response in patients with metastatic cancer. However, germline and clonal hematopoiesis–associated alterations can confound identification of tumor-specific mutations in cell-free DNA (cfDNA), often requiring additional sequencing of tumor tissue. The current study assessed whether ctDNA-based treatment response monitoring could be performed in a tumor tissue–independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC)-derived DNA. Experimental Design: In total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 patients with metastatic colorectal cancer participating in the prospective phase III CAIRO5 clinical trial were analyzed using an ultra-deep targeted sequencing liquid biopsy assay. Results: The combined cfDNA and WBC analysis prevented false-positives due to germline or hematopoietic variants in 40% of patients. Patient-matched tumor tissue sequencing did not provide additional information. Longitudinal analyses of ctDNA were more predictive of overall survival than standard-of-care radiological response evaluation. ctDNA mutations related to primary or acquired resistance to panitumumab were identified in 42% of patients. Conclusions: Accurate calling of ctDNA mutations for treatment response monitoring is feasible in a tumor tissue–independent manner by combined cfDNA and patient-matched WBC genomic DNA analysis. This tissue biopsy-independent approach simplifies sample logistics and facilitates the application of liquid biopsy ctDNA testing for evaluation of emerging therapy resistance, opening new avenues for early adaptation of treatment regimens.
Association Between <scp><i>HLA</i></scp><i>–<scp>DPB1</scp></i> and Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in Children
Authors: Kristen M. Gibson, Britt I. Drögemöller, Dirk Foell, Susanne M. Benseler, Jinko Graham, Robert E. W. Hancock, Raashid A. Luqmani, David A. Cabral, Kelly L. Brown, Colin J. Ross
Journal: Arthritis & Rheumatology (2022)

Objective Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a rare, life‐threatening inflammation of blood vessels that can affect both adults and children. Compared to adult‐onset disease, AAV is especially rare in children, with an annual prevalence of 0.5–6.4 cases per million children. The etiology of AAV remains largely unknown, and both environmental and genetic factors are likely involved. The present study was undertaken to explore the genetic susceptibility factors recently identified in adult patients, including HLA–DP and HLA–DQ, in pediatric patients. Methods We performed a genome‐wide association study of pediatric AAV in patients of European ancestry (n = 63 AAV cases, n = 315 population‐matched controls). Results We identified a significant genetic association between pediatric AAV and the HLA–DPB1*04:01 allele ( P = 1.5 × 10 −8 , odds ratio [OR] 3.5), with a stronger association observed in children with proteinase 3–ANCA positivity than in children with myeloperoxidase−ANCA positivity. Among the HLA alleles, the HLA–DPB1*04:01 allele was the most highly associated with AAV, although not significantly, in a follow‐up adult AAV cohort ( P = 2.6 × 10 −4 , OR 0.4). T cell receptor and interferon signaling pathways were also shown to be enriched in the pediatric AAV cohort. Conclusion The HLA–DPB1 locus showed an association with pediatric AAV, as similarly shown previously in adult AAV. Despite the difference in the age of onset, these findings suggest that childhood‐ and adult‐onset vasculitis share a common genetic predisposition. The identification of genetic variants contributing to AAV is an important step to improved classification tools and treatment strategies.
Acute, Prolonged, and Extensive Myocardial Ischemia in a Patient With Colorectal Cancer
Authors: Stefano Savonitto, Gianmarco Angelini, Andrea Farina
Journal: JAMA Internal Medicine (2022)

This case report describes a patient in their 60s with spontaneously subsiding and reoccurring severe acute chest pain that lasted for about 30 minutes as well as a recent diagnosis of colorectal cancer.
Corrigendum to “Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer”
Authors: K. Van Baelen, T. Geukens, M. Maetens, V. Tjan-Heijnen, C.J. Lord, S. Linn, F.-C. Bidard, F. Richard, W.W. Yang, R.E. Steele, S.J. Pettitt, C. Van Ongeval, M. De Schepper, E. Isnaldi, I. Nevelsteen, A. Smeets, K. Punie, L. Voorwerk, H. Wildiers, G. Floris, A. Vincent Salomon, P.W.B. Derksen, P. Neven, E. Senkus, E. Sawyer, M. Kok, C. Desmedt
Journal: Annals of Oncology (2022)
Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling
Authors: Yan Zhang, Yang Cao, Rui Zheng, Zhenyu Xiong, Zhengru Zhu, Fanya Gao, Wanrong Man, Yu Duan, Jie Lin, Xuebin Zhang, Dexi Wu, Mengyuan Jiang, Xiao Zhang, Congye Li, Xiaoming Gu, Yanhong Fan, Dongdong Sun
Journal: Theranostics (2022)

Rationale: Extracellular matrix (ECM) remodeling, a key pathological feature in diabetic cardiomyopathy (DCM), is triggered by oxidative stress, inflammation, and various metabolic disorders in the heart.Cardiac fibroblasts (CFs) are the primary source of ECM proteins and the ultimate effector cells in ECM remodeling.CFs are turned on and differentiated into myofibroblasts in response to profibrotic signaling.Rnd3 is a small Rho-GTPase involved in the regulation of cell-cycle distribution, cell migration, and cell morphogenesis.Emerging evidence suggests a link between Rnd3 expression and onset of cardiovascular diseases.However, the role of Rnd3 in DCM remains unknown.Methods: Flow cytometry was employed to separate different types of cardiac cells.Type 2 diabetes mellitus was established in Rnd3 fibroblast-specific knockout and transgenic mice.RNA sequencing and chromatin immunoprecipitation assay were used to discern signaling pathways involved.Results: Rnd3 expression was reduced in cardiac tissues of diabetic mice, with CFs being the primary cell type.Fibroblast-specific upregulation of Rnd3 in vivo was protective against DCM, whereas Rnd3 downregulation in fibroblasts accentuated cardiac oxidative stress, fibrosis, ventricular remodeling, and dysfunction.Moreover, in vitro Rnd3 overexpression significantly attenuated reactive oxygen species production, CF migration and proliferation under high levels of glucose (35 mmol/L) and palmitic acid (500 µmol/L) challenge.Furthermore, RNA sequencing indicated that Notch and TGF-β signaling were significantly suppressed upon Rnd3 overexpression.Mechanistically, Rnd3 regulated Notch and TGF-β signaling by interacting with NICD and ROCK1, respectively.Specifically, glucotoxicity and lipotoxicity control Rnd3 expression by regulating the binding of Nr1H2 and Rnd3 promoter.Conclusions: Our findings provide compelling evidence in that fibroblast-specific activation of Rnd3 protects against cardiac remodeling in DCM, indicating promises of targeting Rnd3 in the treatment of DCM.
Time to Change the Current Clinical Classification of Multiple Sclerosis?
Authors: Cristina Granziera, Tobias Derfuss, Ludwig Kappos
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Unintended Consequences of Antibiotic Therapy on the Microbiome Delivers a Gut Punch in Ovarian Cancer
Authors: Shannon M. Hawkins, Kenneth P. Nephew
Journal: Cancer Research (2022)

While the early use of antibiotics during chemotherapy may be lifesaving, antibiotic therapy is associated with worse outcomes in patients with ovarian cancer during platinum chemotherapy. The study by Chambers and colleagues in this issue of Cancer Research provides mechanistic insights into how disrupting the gut microbiome with broad-spectrum antibiotics negatively influences the survival of patients with ovarian cancer and highlights the impact of the gut microbiome on tumor progression and response to therapy. Treatment of ovarian cancer models with a broad-spectrum antibiotic cocktail (ABX, vancomycin, neomycin sulfate, metronidazole, ampicillin) changed the gut microbiome and increased tumor growth and development of cisplatin resistance. Stem cells, reported to drive resistance to chemotherapy and disease recurrence in ovarian cancer, were enriched as a surprising consequence of ABX-induced microbiome disruption. Immune-competent and immune-deficient mice revealed that ABX treatment enhanced the cisplatin-induced stemness and provided evidence for immune surveillance of ovarian cancer stem cells through the gut microbiome. Two gut-derived metabolites, indole-3-propionic acid and indoxyl sulfate, suppressed by ABX treatment and reestablished with cecal microbial transplantation colonization of ABX-treated mice, were identified as potential effectors connecting the gut microbiome to ovarian cancer growth. This clinically relevant study opens new therapeutic opportunities for patients-one aimed at interventions to increase platinum sensitivity and another aimed at preventing the potential adverse effects of broad-spectrum antibiotic treatment. Both represent paradigm changes to standard care. See related article by Chambers et al., p. 4654.
Functional Impairment Preceding Parkinson Disease Diagnosis—What’s in a Prodrome?
Authors: Ian O. Bledsoe, Jun Yu, Aparna Wagle Shukla
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
C9orf72 regulates the unfolded protein response and stress granule formation by interacting with eIF2α
Authors: Wenzhong Zheng, Kexin Wang, Yachen Wu, Ge Yan, Chi Zhang, Zhiqiang Li, Lianrong Wang, Shi Chen
Journal: Theranostics (2022)

Rationale: A C9orf72 hexanucleotide repeat expansion (GGGGCC) is the most common genetic origin of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Haploinsufficiency of C9orf72 has been proposed as a possible disease mechanism (loss-of-function mechanism). Additionally, the aberrantly activated unfolded protein response (UPR) and stress granule (SG) formation are associated with the etiopathology of both ALS and FTD. However, the molecular determinants in this pathogenesis are not well characterized. Methods: We performed an immunoprecipitation-mass spectrometry (IP-MS) assay to identify potential proteins interacting with the human C9orf72 protein. We used C9orf72 knockout cell and rat models to determine the roles of C9orf72 in translation initiation and the stress response. Results: Here, we show that C9orf72, which is genetically and pathologically related to ALS and FTD, interacts with eukaryotic initiation factor 2 subunit alpha (eIF2α) and regulates its function in translation initiation. C9orf72 knockout weakens the interaction between eIF2α and eIF2B5, leading to global translation inhibition. Moreover, the loss of C9orf72 results in primary ER stress with activated UPR in rat spleens, which is one of the causes of splenomegaly with inflammation in C9orf72-/- rats. Finally, C9orf72 delays SG formation by interacting with eIF2α in stressed cells. Conclusions: In summary, these data reveal that C9orf72 modulates translation initiation, the UPR and SG formation, which have implications for understanding ALS/FTD pathogenesis.
<scp>NLRP3</scp> Attenuates Intraocular Inflammation by Inhibiting <scp>AIM2‐Mediated</scp> Pyroptosis Through the Phosphorylated <scp>Salt‐Inducible</scp> Kinase 1/Sterol Regulatory Element Binding Transcription Factor 1 Pathway
Authors: Jiayu Meng, Na Li, Xianyang Liu, Shengjun Qiao, Qian Zhou, Jun Tan, Ting Zhang, Zhifang Dong, Xiaopeng Qi, Aize Kijlstra, Liming Mao, Peizeng Yang, Shengping Hou
Journal: Arthritis & Rheumatology (2022)

The NLRP3 inflammasome has been shown to be involved in the development of uveitis, but the exact mechanism remains elusive. This study was undertaken to explore the role of NLRP3 in the development of uveitis.First, Nlrp3-deficient mice were used to study the role of NLRP3 in experimental autoimmune diseases, such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). Next, the gathering of ASC, activation of caspase 1 and gasdermin D, and secretion of lactate dehydrogenase and interleukin-1β were detected to confirm macrophage pyroptosis and AIM2 activation in the Nlrp3-/- mice. Additionally, RNA sequencing and chromatin immunoprecipitation-polymerase chain reaction were used to investigate the phosphorylated salt-inducible kinase 1 (p-SIK1)/sterol regulatory element binding transcription factor 1 (SREBF1) pathway, which regulates the transcription of Aim2. Finally, overexpression of Nlrp3 was applied to treat EAU.Surprisingly, our findings show that NLRP3 plays an antiinflammatory role in 2 models of EAU and EAE. Additionally, macrophages show an increased M1 activation and pyroptosis in Nlrp3-/- mice. Further experiments indicate that this pyroptosis of macrophages was mediated by the up-regulated transcription of Aim2 as a result of Nlrp3 deficiency. In mechanistic studies, Nlrp3 deficiency was implicated in the down-regulation of p-SIK1 and subsequently the up-regulation of SREBF1, which binds to Aim2 and then promotes the latter's transcription. Finally, Aim2 deficiency, RNA silencing of Aim2 or Srebf1, and overexpression of Nlrp3 resulted in attenuated inflammation of EAU.Our data demonstrate that NLRP3 inhibits AIM2 inflammasome-mediated EAU by regulating the p-SIK1/SREBF1 pathway, highlighting the therapeutic potential of targeting Nlrp3.
Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk
Authors: Arthur J. Sit, Teresa C. Chen, Hana L. Takusagawa, Jullia A. Rosdahl, Ambika Hoguet, Vikas Chopra, Grace M. Richter, Yvonne Ou, Stephen J. Kim, Darrell WuDunn
Journal: Ophthalmology (2022)
Evaluation of a Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) Cartridge Assay for Predicting Early Disease Progression and Survival: TBCRC 005 Prospective Trial
Authors: Kala Visvanathan, Leslie Cope, Mary Jo Fackler, Michael Considine, Lori Sokoll, Lisa A. Carey, Andres Forero-Torres, James N. Ingle, Nancy U. Lin, Rita Nanda, Anna Maria Storniolo, Suzana Tulac, Neesha Venkatesan, Natalie C. Wu, Sudhakar Marla, Scott Campbell, Michael Bates, Christopher B. Umbricht, Antonio C. Wolff, Saraswati Sukumar
Journal: Clinical Cancer Research (2022)

We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC.The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC.At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20-3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77-11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29-5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment.The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.